A Study Exploring the Use of Challenge Agents in Healthy Volunteers - Intervention Specific Appendix

A Phase 0 Platform Study Exploring the Use of Challenge Agents in Healthy Volunteers

The purpose of this study is to characterize the disruption of intestinal barrier as a result of indomethacin challenge in healthy volunteers using an orally administered lactulose-mannitol test.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Indomethacin; Diagnostic test: Lactulose-mannitol

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy on the basis of physical examination, medical history, and vital signs, and 12-lead electrocardiogram (ECG) performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator
• healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
• must be a non-smoker (not smoked for at least 6 months prior to screening) and has not used nicotine-containing products (example, nicotine patch) for 3 months prior to screening
• A woman must be: a) not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than (<1) percent (%) per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until the end of the intervention cohort. The investigator should evaluate the potential for contraceptive method failure (example, noncompliance, recently initiated) in relationship to the first dose of study intervention
• A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test prior to study intervention administration on Day -4

Exclusion Criteria:

• history of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• history of any type of immunodeficiency or autoimmune disease or disease treatment associated with immune suppression or lymphopenia. These include but are not limited to bone marrow or organ transplantation, lymphoproliferative disorders, T- or B-cell deficiency syndromes, splenectomy, functional asplenia and chronic granulomatous disease
• has an active, acute or chronic infection
• has a history of inflammatory bowel disease (IBD), celiac disease, or gastrointestinal diseases (GI) surgery, excluding appendectomy and cholecystectomy
• has known allergies, hypersensitivity, or intolerance to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indomethacin Challenge; Participants will receive challenge agent as two single oral doses of Indomethacin, one on Day -1 and one on Day 1. In addition, participants will receive lactulose-mannitol solution on Day -4 (baseline) and on Day 1 (post Indomethacin challenge).	Drug: Indomethacin; Indomethacin capsules will be administered orally.; Diagnostic test: Lactulose-mannitol; Lactulose-mannitol solution will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Change From Baseline in Lactulose/Mannitol Ratio in the Urine Following Indomethacin Challenge	Longitudinal change from baseline in L/M ratio in the urine following indomethacin challenge will be assessed. L/M ratio in urine is a useful and noninvasive marker for the evaluation of intestinal permeability in the urinary excretion of these nonmetabolized sugars.	Baseline, Up to 14 days
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 6 weeks
Number of Participants with Treatment-Emergent Serious Adverse Events (TE-SAEs)	TE-SAEs is defined as any untoward medical occurrence with a reasonable possibility that it is caused by the study intervention that: Is life-threatening (example; leads to stroke or non-fatal pulmonary embolism); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Results in other clinically significant sign(s) or symptom(s), (example; clinically asymptomatic brain microhemorrhages); or Results in death.	Up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Change From Baseline in Selected Biomarkers Following Indomethacin Challenge	Change from baseline in selected biomarkers levels (example: Lactulose-mannitol, C-reactive protein [CRP], calprotectin, Et cetera [etc.]) using analysis methods such as liquid chromatography/mass spectrometry, immunoturbidimetry, enzyme-linked immunosorbent assay (ELISA), etc., as a result of the indomethacin challenge.	Baseline, Up to 14 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): May 7, 2021
• Study Completion (Actual): May 7, 2021

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Lactulose; Mannitol; Indomethacin
• Other Study ID Numbers: CR108965; NOPRODPCNAP0001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No